Crucell Terug naar discussie overzicht

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1. flosz 15 maart 2008 15:44

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   J Virol. 2008 Mar 12
   
   Magnitude and Phenotype of Cellular Immune Responses Elicited by Recombinant Adenovirus Vectors and Heterologous Prime-Boost Regimens in Rhesus Monkeys.
   
   Liu J, Ewald BA, Lynch DM, Denholtz M, Abbink P, Lemckert AA, Carville A, Mansfield KG, Havenga MJ, Goudsmit J, Barouch DH.
   Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; Crucell Holland BV, 2301 CA, Leiden, The Netherlands; New England Primate Research Center, Southborough, MA 01772.
   
   Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for HIV-1 and other pathogens have been shown to elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have also been constructed to circumvent pre-existing anti-Ad5 immunity and to facilitate the development of novel heterologous rAd prime-boost regimens. Here we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct phenotypes of cellular immune responses in rhesus monkeys and can be combined as potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced primarily IFN-gamma+ and IFN-gamma+/TNF-alpha+ T lymphocyte responses, rAd26-Gag and rAd48-Gag induced higher proportions of IL-2+ and polyfunctional IFN-gamma+/TNF-alpha+/IL-2+ T lymphocyte responses. Priming with the rare serotype rAd vectors proved remarkably effective for subsequent boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd vectors elicited phenotypically distinct T lymphocyte responses as compared with rAd5 vectors and suggest the functional relevance of polyfunctional CD8+ and CD4+ T lymphocyte responses. Moreover, qualitative differences in cellular immune responses may prove critical in determining the overall potency of heterologous rAd prime-boost regimens.
   PMID: 18337575
   
   www.ncbi.nlm.nih.gov/pubmed/18337575?...
   *********************************
   
   Impact of recombinant Ad35 priming versus boosting of a Plasmodium falciparum protein: characterization of T- and B-cell responses to the liver stage antigen 1 (LSA-1).
   
   Rodríguez A, Goudsmit J, Companjen A, Mintardjo R, Gillissen G, Tax D, Sijtsma J, Weverling GJ, Holterman L, Lanar DE, Havenga MJ, Radosevic K.
   Crucell Holland BV, PO Box 2048, 2301 CA Leiden, the Netherlands; Center of Poverty-related Communicable Diseases Academic Medical Center, Amsterdam, The Netherlands; Divison of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500.
   
   Prime-boost vaccination regimens with heterologous antigen delivery systems have indicated that redirection of the immune response is feasible. We showed earlier that T-cell responses to circumsporozoite protein improved significantly when the protein is primed with rAd35.CS. The current study was designed to answer the question whether such an effect can be extended to liver stage antigens of Plasmodium falciparum like LSA-1. Studies in mice have demonstrated that the LSA-1 protein induces strong antibody response but a weak T-cell immunity. We first identified T-cell epitopes in LSA-1 using intracellular IFN-gamma staining, and confirmed these epitopes by means of ELISPOT and pentamer staining. We show that a single immunization with rAd35.LSA-1 induced a strong antigen-specific IFN-gamma CD8(+) T-cell response, but no measurable antibody response. In contrast, vaccinations with the adjuvanted recombinant LSA-1 protein induced remarkably low cellular responses but strong antibody responses. Finally, both priming and boosting of the adjuvanted protein by the rAd35 resulted in enhanced T-cell responses without impairing the level of antibody responses induced by the protein immunizations alone. Furthermore, the incorporation of rAd35 in the vaccination schedule led to a skewing of LSA-1 specific antibody responses towards a Th1 type immune response. Our results show the ability of recombinant Ad35 to induce potent T-cell immunity in combination with protein in a prime-boost schedule, without impairing the B-cell response.
   PMID: 18212075
   
   www.ncbi.nlm.nih.gov/pubmed/18212075?...
   
2. flosz 19 maart 2008 16:18

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   Vaccine. 2008 Feb 22
   
   Induction of neutralising antibodies and cellular immune responses against SARS coronavirus by recombinant measles viruses.
   
   Liniger M, Zuniga A, Tamin A, Azzouz-Morin TN, Knuchel M, Marty RR, Wiegand M, Weibel S, Kelvin D, Rota PA, Naim HY.
   Berna Biotech (a Crucell Company), Rehhagstrasse 79, CH-3018 Bern, Switzerland.
   
   Live attenuated recombinant measles viruses (rMV) expressing a codon-optimised spike glycoprotein (S) or nucleocapsid protein (N) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) were generated (rMV-S and rMV-N). Both recombinant viruses stably expressed the corresponding SARS-CoV proteins, grew to similar end titres as the parental strain and induced high antibody titres against MV and the vectored SARS-CoV antigens (S and N) in transgenic mice susceptible to measles infection. The antibodies induced by rMV-S had a high neutralising effect on SARS-CoV as well as on MV. Moreover, significant N-specific cellular immune responses were measured by IFN-gamma ELISPOT assays. The pre-existence of anti-MV antibodies induced by the initial immunisation dose did not inhibit boost of anti-S and anti-N antibodies. Immunisations comprising a mixture of rMV-S and rMV-N induced immune responses similar in magnitude to that of vaccine components administered separately. These data support the suitability of MV as a bivalent candidate vaccine vector against MV and emerging viruses such as SARS-CoV.
   PMID: 18346823
   www.ncbi.nlm.nih.gov/pubmed/18346823?...
   
3. flosz 3 mei 2008 15:13

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   J Virol. 2008 Apr 30
   
   Differential Antigen Requirements for Protection Against Systemic and Intranasal Vaccinia Virus Challenges in Mice.
   
   Kaufman DR, Goudsmit J, Holterman L, Ewald BA, Denholtz M, Devoy C, Giri A, Grandpre LE, Heraud JM, Franchini G, Seaman MS, Havenga MJ, Barouch DH.
   Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; Crucell Holland BV, 2301 CA, Leiden, The Netherlands; National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
   
   The development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. Preclinical studies to date with subunit smallpox vaccine candidates, however, have been limited by incomplete information regarding protective antigens and the requirement for multiple boost immunizations to afford protective immunity. Here we explore the protective efficacy of replication-incompetent, recombinant adenovirus serotype 35 (rAd35) vectors expressing the vaccinia intracellular mature virion (IMV) antigens A27L and L1R and extracellular enveloped virion (EEV) antigens A33R and B5R in a murine vaccinia challenge model. A single immunization with the rAd35-L1R vector effectively protected mice against a lethal systemic vaccinia challenge. The rAd35-L1R vector also proved more efficacious than the combination of four rAd35 vectors expressing A27L, L1R, A33R, and B5R. Moreover, serum containing L1R-specific neutralizing antibodies (NAbs) afforded post-exposure prophylaxis following systemic vaccinia infection. In contrast, the combination of rAd35-L1R and rAd35-B5R vectors was required to protect mice against a lethal intranasal vaccinia challenge, suggesting that both IMV- and EEV-specific immune responses are important following intranasal infection. Taken together, these data demonstrate that different protective antigens are required based on the route of vaccinia challenge. These studies also suggest that rAd vectors warrant further assessment as candidate subunit smallpox vaccines.
   PMID: 18448519
   
   www.ncbi.nlm.nih.gov/pubmed/18448519?...
   
4. flosz 7 mei 2008 18:36

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   Interessant imo…J. Cohen als in GSK’S RTS,S/AS02A J. Cohen………
   
   Vaccine. 2008 Apr 16
   Adenovirus 5 and 35 vectors expressing Plasmodium falciparum circumsporozoite surface protein elicit potent antigen-specific cellular IFN-gamma and antibody responses in mice.
   
   Shott JP, McGrath SM, Pau MG, Custers JH, Ophorst O, Demoitié MA, Dubois MC, Komisar J, Cobb M, Kester KE, Dubois P, Cohen J, Goudsmit J, Heppner DG, Stewart VA.
   Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, USA.
   
   Falciparum malaria vaccine candidates have been developed using recombinant, replication-deficient serotype 5 and 35 adenoviruses (Ad5, Ad35) encoding the Plasmodium falciparum circumsporozoite surface protein (CSP) (Ad5.CS, Ad35.CS) (Crucell Holland BV, Leiden, The Netherlands). To evaluate the immunogenicity of these constructs, BALB/cJ mice were immunized twice with either Ad5.CS, Ad35.CS, empty Ad5-vector (eAd5), empty Ad35 vector (eAd35), or saline. Another group received the CSP-based RTS,S malaria vaccine formulated in the proprietary Adjuvant System AS01B (GlaxoSmithKline Biologicals, Rixensart, Belgium). Here we report that Ad5.CS, Ad35.CS, and RTS,S/AS01B, elicited both cellular and serologic CSP antigen-specific responses in mice. These adenoviral vectors induce strong malaria-specific immunity and warrant further evaluation.
   PMID: 18455276
   www.ncbi.nlm.nih.gov/pubmed/18455276?...
   
   (Dr. Joe Cohen, one of the inventors and original patent holder of the RTS,S/AS02A malaria vaccine, joined GSK Bio in 1984)
   
5. flosz 7 mei 2008 19:16

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   Nog even tussen haakjes…..
   GSK announces changes to Corporate Executive Team
   
   Issued: 30th April 2008, London, UK and Philadelphia, USA
   GlaxoSmithKline (GSK) today announced a number of changes to its Corporate Executive management team. In a message to employees, Andrew Witty, CEO designate, detailed new appointments and his new management team which will take effect on 22nd May when he assumes the role of Chief Executive Officer.
   Outlining the context for these changes, Andrew Witty said: “It is clear that our industry is facing a rapidly changing environment. Demand for innovative medicines and healthcare products continues to grow, however we are also presented with increasing challenges, such as cost containment, regulatory pressures and generic competition.”
   To address these challenges, Witty stated that the company must work hard to increase GSK’s global reach and presence, and ensure that vaccines, consumer healthcare and pharmaceuticals all play their full potential.
   crucell.yourbb.nl/viewtopic.php?f=26&...
   
   Mmmmm….geen gentlemen’s agreement maar een geregistreerd partnerschap…een malariahuwelijk, ook lekker…… wait and see.
   www.thetrebleshooters.nl/songs/talkin...
   
6. [verwijderd] 7 mei 2008 20:49

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   Flosz, wellicht enige pressie van Amerikanen, waar ze beide mee werken, om toch maar samen verder te gaan?
7. flosz 8 mei 2008 09:26

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   Idd. mogelijk, Crucell & GSK zijn imo in staat SAMEN iets heel moois te maken. Ik zou Maria Pau wel eens willen horen mbt. aanvulling Crucell<>GSK.
   *************************
   
   For a malaria vaccine to be used in a national programme, it has to be 70% effective or more. Using a mosquito net alone gives 60% protection.
   ******************************
   In March 2003, we entered into collaboration with the Walter Reed Army Institute of Research (WRAIR) and GlaxoSmithKline Biologicals (GSK) under a Cooperative Research and Development Agreement (CRADA). In line with this agreement, we have completed work with WRAIR and GSK to evaluate our AdVac® malaria vaccine candidate. Our vaccine candidate was tested as a stand-alone vaccine and in combination with GSK’s RTS,S malaria vaccine candidate. These studies have shown that Crucell’s AdVac® vaccine candidate efficiently primed and/or boosted malaria specific immune responses.
   
   The GSK malaria vaccine candidate RTS,S has, as a stand-alone vaccine, been shown to confer partial protection to human volunteers in both a laboratory challenge model conducted at WRAIR and under natural challenge conditions in a field study conducted in the Gambia. Phase IIb pediatric trials conducted with RTS,S in Mozambique and reported in The Lancet medical journal in October 2004 and 2007 demonstrated further promising results, with the vaccine protecting some infants against infection and making the course of the disease less serious and life threatening in others.
   
   In March 2004 it was announced that the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH), will support the development of our candidate malaria vaccine. The agreement has an estimated value of up to US$ 3.5 million and covers process development of the candidate AdVac-based malaria vaccine including the production of clinical trial material and Investigational New Drug (IND) filing. The work is being done under a subcontract agreement with Science Applications International Corporation (SAIC).
   
   In partnership with the NIAID, Crucell’s malaria vaccine entered a Phase I trial in the US in Q4 2006. The study is being carried out on two sites, VanderBilt and Stanford University. The first and second cohorts, comprising 18 and 17 volunteers respectively, have been successfully enrolled. No serious adverse side-effects have been reported to date. Current plans call for subsequent enrollment of two additional cohorts at higher vaccine doses, provided the vaccine has an appropriate safety profile. Following review of the safety data by a Safety Monitoring Committee, a decision has been made to begin recruitment of the third cohort. Initial findings of this Phase I trial are expected to be available in 2008.
   
   **********************
   
   Uit post aossa, okt. 2007:
   Is het geen noodzaak dat Crucell vaccine tesamen met het GSK wordt ontwikkeld en/of goedgekeurd. Eens het Ad35 van Crucell stand-alone goedgekeurd, zou het in een combinatie 'extended application' extra waarde (betere immuun respons) kunnen geven aan het GSK RTS, S vaccine, waarbij het Ad35 vaccine als eerste wordt toegediend en de T-cel immuniteit activeert ten voordele van de 2 volgende inentingen met het GSK vaccine. Respons >90% ipv 65% !
   Meer via:
   crucell.yourbb.nl/viewtopic.php?f=7&t...
   
8. aossa 8 mei 2008 09:39

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   Plaatje erbij (uit post okt 2007)
   
   /quote
   Zoals ik het begrijp uit het plaatje
   
   Plaatje zie: img.iex.nl/ForumUploads/2796346.jpg
   Analyst meeting 24/11/2006
   
   Is het geen noodzaak dat Crucell vaccine tesamen met het GSK wordt ontwikkeld en/of goedgekeurd.
   
   Eens het Ad35 van Crucell stand-alone goedgekeurd, zou het in een combinatie 'extended application' extra waarde (betere immuun respons) kunnen geven aan het GSK RTS, S vaccine, waarbij het Ad35 vaccine als eerste wordt toegediend en de T-cel immuniteit activeert ten voordele van de 2 volgende inentingen met het GSK vaccine. Respons >90% ipv 65% ! /
   
   Just an humble opinion !
9. [verwijderd] 8 mei 2008 10:22

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   Het punt is alleen , dat je dat met 2 bokken , niet voor elkaar krijgt.
10. flosz 8 mei 2008 11:22

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    quote:

    wilb52 schreef:

    Het punt is alleen , dat je dat met 2 bokken , niet voor elkaar krijgt.
    

    Misschien staan er nu bij GSK een paar geiten klaar....
    Bok+sik=lam/bok+sikjes=veul lammekes.
11. aossa 8 mei 2008 11:27

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    WHO an PAHO heeft in deze imo het laatste woord.
    Wanneer die beslissen om 2 'bestaande stand-alone vaccines' in een 'combinatie- therapie' toe te passen, welke bok gaat dat tegenhouden ?
    
    Simpelweg:
    1e vaccinatie: Crucell Ad35 vaccine (als booster)
    1 maand later 1e GSK vaccine
    3 maand later 2e GSK vaccine als rappel
    
    90% respons ipv 65%
    
    Iedereen tevreden !
    

    Bijlage:
12. flosz 18 mei 2008 13:38

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    quote:

    flosz schreef:

    Interessant imo…J. Cohen als in GSK’S RTS,S/AS02A J. Cohen………
    
    Vaccine. 2008 Apr 16
    Adenovirus 5 and 35 vectors expressing Plasmodium falciparum circumsporozoite surface protein elicit potent antigen-specific cellular IFN-gamma and antibody responses in mice.
    
    Shott JP, McGrath SM, Pau MG, Custers JH, Ophorst O, Demoitié MA, Dubois MC, Komisar J, Cobb M, Kester KE, Dubois P, Cohen J, Goudsmit J, Heppner DG, Stewart VA.
    Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD, 20910, USA.
    
    Falciparum malaria vaccine candidates have been developed using recombinant, replication-deficient serotype 5 and 35 adenoviruses (Ad5, Ad35) encoding the Plasmodium falciparum circumsporozoite surface protein (CSP) (Ad5.CS, Ad35.CS) (Crucell Holland BV, Leiden, The Netherlands). To evaluate the immunogenicity of these constructs, BALB/cJ mice were immunized twice with either Ad5.CS, Ad35.CS, empty Ad5-vector (eAd5), empty Ad35 vector (eAd35), or saline. Another group received the CSP-based RTS,S malaria vaccine formulated in the proprietary Adjuvant System AS01B (GlaxoSmithKline Biologicals, Rixensart, Belgium). Here we report that Ad5.CS, Ad35.CS, and RTS,S/AS01B, elicited both cellular and serologic CSP antigen-specific responses in mice. These adenoviral vectors induce strong malaria-specific immunity and warrant further evaluation.
    PMID: 18455276
    www.ncbi.nlm.nih.gov/pubmed/18455276?...
    
    (Dr. Joe Cohen, one of the inventors and original patent holder of the RTS,S/AS02A malaria vaccine, joined GSK Bio in 1984)
    
    

    Uit: Malaria: The end of the beginning
    Hill's doubts about the vaccine bolster a more general frustration with what he sees as GSK's go-it-alone approach, “unconnected to the other 12 or 15 groups developing vaccines” (see table 1). He and others want different vaccines to be combined with RTS,S in Phase II testing, suspecting efficacy might be greatly enhanced. Heppner, for example, says that results of studies he and his colleagues have carried out on macaques indicate that combining an adenovirus-based vaccine made by the Netherlands biotech company CruCell with RTS,S would offer much better effects[10]: “My hope is that a way can be found to evaluate this clinically just as we've done for earlier improvements of RTS,S.” Ballou says that although progress in studying this combination has been stalled for “various business reasons”, several collaborative efforts continue.
    
    Volledig art.: crucell.yourbb.nl/viewtopic.php?f=7&t...
    
13. flosz 21 mei 2008 22:18

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    doi:10.1016/j.vaccine.2008.03.083
    Copyright © 2008 Elsevier Ltd All rights reserved.
    
    EV01: A phase I trial in healthy HIV negative volunteers to evaluate a clade C HIV vaccine, NYVAC-C undertaken by the EuroVacc Consortium
    
    Pierre-Alexandre Bart, Ruth Goodall, Tristan Barber, Alexandre Harari, Ana Guimaraes-Walker, Mona Khonkarly, Neil C. Sheppard, Yolanda Bangala, Marie-Joelle Frachette, Ralf Wagner, Peter Liljeström, Jean-Pierre Kraehenbuhl, Marc Girard, Jaap Goudsmit , Mariano Esteban, Jonathan Heeney, Quentin Sattentau, Sheena McCormack, Abdel Babiker, Giuseppe Pantaleo and Jonathan Weber
    
    Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
    MRC Clinical Trials Unit, 222 Euston Road, London NW1 2DA, UK
    St. Mary's Hospital, London, UK
    University of Oxford, Oxford, UK
    Sanofi Pasteur, Lyon, France
    University of Regensburg, Regensburg, Germany
    Karolinska Institutet, Stockholm, Sweden
    Eurovacc Foundation, Lausanne, Switzerland
    Centre National de la Recherche Scientifique, Lyon, France
    Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
    Centro Nacional de Biotecnologia, Madrid, Spain
    Biomedical Primate Research Centre, Rijswijk, The Netherlands
    
    Received 14 March 2008;
    accepted 19 March 2008.
    Available online 17 April 2008.
    NYVAC HIV-C (vP2010), a recombinant vector expressing HIV subtype C gag, pol, env and nef antigens, was tested in a phase I study in healthy, HIV negative volunteers in London and Lausanne. Twenty-four participants were randomised to receive NYVAC-C (20) or matching placebo (4) at weeks 0 and 4, and assessed for safety and immunogenicity over 48 weeks. There were no serious adverse events, and no clinical or laboratory abnormalities or other events that led to withdrawal, interruption or dose reduction of the NYVAC-C/placebo. Half of the 10 assessed responded in the ELISpot assay under stringent criteria, which informed the sample size for a DNA–NYVAC-HIVC comparison to NYVAC-HIVC alone.
    www.sciencedirect.com
14. flosz 21 mei 2008 22:20

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    doi:10.1016/j.vaccine.2008.04.071
    Copyright © 2008 Published by Elsevier Ltd.
    
    Antibody and T-cell responses to a virosomal adjuvanted H9N2 avian influenza vaccine: Impact of distinct additional adjuvants
    
    Katarina Radošević, Ariane Rodriguez, Ratna Mintardjo, Dennis Tax, Karin Lövgren Bengtsson, Catherine Thompson, Maria Zambon, Gerrit Jan Weverling, Fons UytdeHaag and Jaap Goudsmit
    
    Crucell Holland BV, Leiden, The Netherlands
    Isconova AB, Uppsala, Sweden
    Health Protection Agency, London, United Kingdom
    Center of Poverty-related Communicable Diseases, Academic Medical Center, Amsterdam, The Netherlands
    
    Received 8 February 2008;
    revised 11 April 2008;
    accepted 28 April 2008.
    Available online 15 May 2008.
    
    A highly efficacious vaccine is required to counteract a threat of an avian influenza pandemic. Increasing the potency of vaccines by adjuvation is essential not only to overcome generally low immunogenicity of pandemic strains, but also to allow dose sparing and as such to make it feasible to satisfy huge global production demands. In this study we evaluated the ability of four distinct adjuvants to further increase immune responses to a virosomal adjuvanted avian H9N2 influenza vaccine in mice. Currently registered adjuvants aluminium phosphate, aluminium hydroxide and MF59, as well as a novel promising adjuvant MATRIX-M were included in the study. Our results demonstrate that all adjuvants significantly increased the H9N2 haemagglutinin (HA) inhibition and ELISA antibody titers induced with the virosomal adjuvanted vaccine. The adjuvants exhibited different effect on the isotype of virus specific antibodies, with MATRIX-M inducing the most pronounced skewing to IgG2a, i.e. towards Th1 type of response. While the virosomal adjuvanted pandemic influenza vaccine efficiently induced CD4+ T-cell response, with no further increase upon adjuvation, the CD8+ T-cell responses induced with virosomal adjuvanted vaccine could be significantly improved upon additional adjuvation with MATRIX-M or MF59. All adjuvants demonstrated a dose sparing effect, i.e. in combination with the virosomal adjuvanted pandemic influenza vaccine they increased immune responses to comparable level independent of the tested vaccine dose.
    In conclusion, our results demonstrate that immune responses to a virosomal adjuvanted pandemic influenza vaccine can be further enhanced by add-on adjuvants, with MATRIX-M being overall the most potent adjuvant in combination with virosomes, followed by MF59 and finally aluminium-based adjuvants.
    www.sciencedirect.com
15. flosz 21 mei 2008 22:40

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    quote:

    flosz schreef:

    Isconova AB, Uppsala, Sweden
    

    hugin.info/132631/R/1088751/191239.pdf
    Pagina 66 en 67.
    
    The project allows for ‘robust scale-up of
    vaccine production’, being coordinated by the
    leading group in virosomal technology – Crucell
    ec.europa.eu/research/health/poverty-...
    
    crucell.yourbb.nl/viewtopic.php?t=63
    
16. [verwijderd] 22 mei 2008 00:11

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    nieuwe adjuvant (MATRIX-M) voor (Berna/Crucell) griep vaccin.
    Beste Flosz, hartelijk dank voor het plaatsen.
    
    Het kan haast niet anders of Crucell gaat haar huidige virosome griep vaccin verder verbeteren met de nieuw onderzochte adjuvant.
17. flosz 4 juni 2008 17:19

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    Biotechnol Bioeng. 2008 Jun 1;100(2):273-83
    Serum-free transient protein production system based on adenoviral vector and PER.C6 technology: high yield and preserved bioactivity.
    
    Havenga MJ, Holterman L, Melis I, Smits S, Kaspers J, Heemskerk E, van der Vlugt R, Koldijk M, Schouten GJ, Hateboer G, Brouwer K, Vogels R, Goudsmit J.
    Crucell Holland BV, PO Box 2048, 2301CA Leiden, The Netherlands. m.havenga@crucell.com
    
    Stable E1 transformed cells, like PER.C6, are able to grow at scale and to high cell densities. E1-deleted adenoviruses replicate to high titer in PER.C6 cells whereas subsequent deletion of E2A from the vector results in absence of replication in PER.C6 cells and drastically lowers the expression of adenovirus proteins in such cells. We therefore considered the use of an DeltaE1/DeltaE2 type 5 vector (Ad5) to deliver genes to PER.C6 cells growing in suspension with the aim to achieve high protein yield. To evaluate the utility of this system we constructed DeltaE1/DeltaE2 vector carrying different classes of protein, that is, the gene coding for spike protein derived from the Coronavirus causing severe acute respiratory syndrome (SARS-CoV), a gene coding for the SARS-CoV receptor or the genes coding for an antibody shown to bind and neutralize SARS-CoV (SARS-AB). The DeltaE1/DeltaE2A-vector backbones were rescued on a PER.C6 cell line engineered to constitutively over express the Ad5 E2A protein. Exposure of PER.C6 cells to low amounts (30 vp/cell) of DeltaE1/DeltaE2 vectors resulted in highly efficient (>80%) transduction of PER.C6 cells growing in suspension. The efficient cell transduction resulted in high protein yield (up to 60 picogram/cell/day) in a 4 day batch production protocol. FACS and ELISA assays demonstrated the biological activity of the transiently produced proteins. We therefore conclude that DeltaE1/DeltaE2 vectors in combination with the PER.C6 technology may provide a viable answer to the increasing demand for high quality, high yield recombinant protein.
    PMID: 18512821
    www.ncbi.nlm.nih.gov/pubmed/18512821?...
    
18. [verwijderd] 4 juni 2008 18:27

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    Flosz je bent weer helemaal op dreef. AB
19. [verwijderd] 5 juni 2008 10:07

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    quote:

    flosz schreef:

    [quote=wilb52]
    Het punt is alleen , dat je dat met 2 bokken , niet voor elkaar krijgt.
    [/quote]
    Misschien staan er nu bij GSK een paar geiten klaar....
    Bok+sik=lam/bok+sikjes=veul lammekes.
    

    Crucell heeft na clinical phase I mbt rabies een betere deal kunnen sluiten met Sanofi.
    Ik ben ervan overtuigd dat dezelfde strategie voor malaria vaccin geldt. Crucell wil eerst waarde toevoegen middels phase I en misschien phase II. Als de resultaten verbluffend zijn kan crucell veel meer vragen aan de mogelijke partner GSK. GSK is dan ook bereid om meer te betalen.
    
    Sammie ik ken je mening in deze. Maar ik heb liever een GSK malaria deal over een jaar welke uiteindelijk miljoenen meer oplevert dan dat je nu een deal zou sluiten.
    Het scheelt enorm veel als je bijvoorbeeld royalty% wijzigt van bijv. 5% naar 15%. Crucell heeft exclusieve licentie voor griepvaccin al te goedkoop verkocht aan Sanofi, dat weet nu wel iedereen....
20. [verwijderd] 5 juni 2008 10:17

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    We therefore conclude that DeltaE1/DeltaE2 vectors in combination with the PER.C6 technology may provide a viable answer to the increasing demand for high quality, high yield recombinant protein.
    

    Dit klinkt VET!